From N-WASP to WAVE: Key Molecules for Regulation of Cortical Actin Organization

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Tadaomi Takenawa

Published Online: 7 OCT 2008

DOI: 10.1002/047001766X.ch2

Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269

Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269

How to Cite

Takenawa, T. (2005) From N-WASP to WAVE: Key Molecules for Regulation of Cortical Actin Organization, in Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269 (eds G. Bock and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/047001766X.ch2

Author Information

  1. Department of Biochemistry, Institute of Medical Science, University of Tokyo and CREST, Japan Science and Technology Corporation (JST), 4-6-1 Shirokanedai, Mianato-ku, Tokyo 108-8639, Japan

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 9 SEP 2005

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470011904

Online ISBN: 9780470017661

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Keywords:

  • N-WASP;
  • WHD (WASP homology domain);
  • GBD/CRIB domain;
  • novel adaptor protein;
  • Ash (abundant SH);
  • N-WASP (neural Wiskott–Aldrich syndrome protein);
  • VCA region;
  • PDGF-coated heparin beads

Summary

We first isolated N-WASP as one of the proteins bound to Ash/Grb2 SH3 domain. This protein has a VCA region (verplorin-like, cofilin-like, acidic region) at the C-terminus, which binds to G-actin and Arp2/3 complex, and several functional domains at the N-terminus, such as WHD (WASP homology domain) and GBD/CRIB domain. N-WASP activates Arp2/3 complex-dependent actin polymerization through the VCA region, leading to filopodium formation. Next, we found WAVE1, WAVE2 and WAVE3. All these proteins have also VCA regions at C-terminal areas and induce membrane ruffle formation. To clarify the different roles of WAVE1 and WAVE2, we established WAVE1- and WAVE2-deficient mouse embryonic fibroblasts (MEFs), because these two WAVEs are expressed in MEF. When wild-type MEFs are stimulated randomly by PDGF, two types of ruffles, peripheral and dorsal, are formed. However, dorsal ruffle formation does not occur in WAVE1-deficient MEFs. In contrast, peripheral ruffle formation is diminished in WAVE2-deficient MEFs. On the other hand, in MEFs migrating towards a chemoattractant gradient, only peripheral ruffles (lamellipodia) are formed. In this migration, WAVE1-deficient MEFs still could form lamellipodia but WAVE2-deficient MEFs could not. All these data show that WAVE2 but not WAVE1 is essential for lamellipodium formation and directed migration.